ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells (2024)

Abstract

ETYA (5,8,11,14-eicosatetraynoic acid), an arachidonic acid analogue, inhibited DNA synthesis in human transformed U937 (monoblastoid), PC3 (prostate) and A172 (glioblastoma) cells, and partially differentiated the U937 and A172 lines. The agent is not primarily cytotoxic at the concentrations employed, based upon exclusion of trypan blue, continued attachment of PC3 and A172 cells, unchanged release of Cr51, and reversibility of inhibited thymidine incorporation after removal of ETYA. Leukotriene C4 partially reversed the suppression of U937 DNA synthesis, suggesting its modulation by leukotrienes. U937 and A172 cells partially differentiated, as judged by a number of criteria. ETYA increased whole cell and microsomal membrane fluidity, increased intracellular Ca2+ in PC3 and U937 cells, altered the distribution and activity of protein kinase C in U937 cells, and rapidly downregulated the transcription of U937 c-myc. Evidence from transmission electron microscopy consistent with oxidative stress including putative lipofuscin bodies, myelin figures and disordered mitochondrial cristae and matrices was especially evident in PC3 cells, less so in A172 and essentially absent in U937 cells. A specific 5′-lipoxygenase inhibitor, A63162 inhibited PC3 and U937 proliferation. Some of these events are believed to represent components of "signal" transduction pathways responsible for reversible inhibition of DNA synthesis and the induction of partial phenotypic differentiation in competent cells. Arachidonic acid analogues which exert selective effects on physical and functional properties of cell membranes may represent an additional class of membrane-active agents with potential anticancer activity. A subset of their activities can be duplicated by inhibitors of 5′ lipoxygenase.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalClinical Biochemistry
Volume25
Issue number1
DOIs
StatePublished - Feb 1992

Keywords

  • AA
  • ASA
  • CAD
  • CL
  • DMSO
  • ETYA 5,8,11,14-eicosatetraynoic acid
  • GFAP
  • HPLC
  • LTC 4
  • PUFA
  • SOD
  • TLC
  • TPN-DPH
  • acetylsalicylic acid
  • arachidonic acid
  • cell division
  • chemiluminescence
  • computer-aided design
  • dimethylsulfoxide
  • glial fibrillary acidic protein
  • high-performance liquid chromatography
  • leukotriene C4
  • polyunsaturated fatty acid
  • superoxide dismutase
  • thin-layer chromatography
  • trimethyl ammonium diphenylhexatriene
  • unsaturated fatty acids (ETYA)

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  • ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells (1)

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Anderson, K. M., Ondrey, F., & Harris, J. E. (1992). ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells. Clinical Biochemistry, 25(1), 1-9. https://doi.org/10.1016/0009-9120(92)80038-I

ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells. / Anderson, Ken M.; Ondrey, Frank; Harris, Jules E.
In: Clinical Biochemistry, Vol. 25, No. 1, 02.1992, p. 1-9.

Research output: Contribution to journalArticlepeer-review

Anderson, KM, Ondrey, F & Harris, JE 1992, 'ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells', Clinical Biochemistry, vol. 25, no. 1, pp. 1-9. https://doi.org/10.1016/0009-9120(92)80038-I

Anderson KM, Ondrey F, Harris JE. ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells. Clinical Biochemistry. 1992 Feb;25(1):1-9. doi: 10.1016/0009-9120(92)80038-I

Anderson, Ken M. ; Ondrey, Frank ; Harris, Jules E. / ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells. In: Clinical Biochemistry. 1992 ; Vol. 25, No. 1. pp. 1-9.

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title = "ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells",

abstract = "ETYA (5,8,11,14-eicosatetraynoic acid), an arachidonic acid analogue, inhibited DNA synthesis in human transformed U937 (monoblastoid), PC3 (prostate) and A172 (glioblastoma) cells, and partially differentiated the U937 and A172 lines. The agent is not primarily cytotoxic at the concentrations employed, based upon exclusion of trypan blue, continued attachment of PC3 and A172 cells, unchanged release of Cr51, and reversibility of inhibited thymidine incorporation after removal of ETYA. Leukotriene C4 partially reversed the suppression of U937 DNA synthesis, suggesting its modulation by leukotrienes. U937 and A172 cells partially differentiated, as judged by a number of criteria. ETYA increased whole cell and microsomal membrane fluidity, increased intracellular Ca2+ in PC3 and U937 cells, altered the distribution and activity of protein kinase C in U937 cells, and rapidly downregulated the transcription of U937 c-myc. Evidence from transmission electron microscopy consistent with oxidative stress including putative lipofuscin bodies, myelin figures and disordered mitochondrial cristae and matrices was especially evident in PC3 cells, less so in A172 and essentially absent in U937 cells. A specific 5′-lipoxygenase inhibitor, A63162 inhibited PC3 and U937 proliferation. Some of these events are believed to represent components of {"}signal{"} transduction pathways responsible for reversible inhibition of DNA synthesis and the induction of partial phenotypic differentiation in competent cells. Arachidonic acid analogues which exert selective effects on physical and functional properties of cell membranes may represent an additional class of membrane-active agents with potential anticancer activity. A subset of their activities can be duplicated by inhibitors of 5′ lipoxygenase.",

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author = "Anderson, {Ken M.} and Frank Ondrey and Harris, {Jules E.}",

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T1 - ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells

AU - Anderson, Ken M.

AU - Ondrey, Frank

AU - Harris, Jules E.

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N2 - ETYA (5,8,11,14-eicosatetraynoic acid), an arachidonic acid analogue, inhibited DNA synthesis in human transformed U937 (monoblastoid), PC3 (prostate) and A172 (glioblastoma) cells, and partially differentiated the U937 and A172 lines. The agent is not primarily cytotoxic at the concentrations employed, based upon exclusion of trypan blue, continued attachment of PC3 and A172 cells, unchanged release of Cr51, and reversibility of inhibited thymidine incorporation after removal of ETYA. Leukotriene C4 partially reversed the suppression of U937 DNA synthesis, suggesting its modulation by leukotrienes. U937 and A172 cells partially differentiated, as judged by a number of criteria. ETYA increased whole cell and microsomal membrane fluidity, increased intracellular Ca2+ in PC3 and U937 cells, altered the distribution and activity of protein kinase C in U937 cells, and rapidly downregulated the transcription of U937 c-myc. Evidence from transmission electron microscopy consistent with oxidative stress including putative lipofuscin bodies, myelin figures and disordered mitochondrial cristae and matrices was especially evident in PC3 cells, less so in A172 and essentially absent in U937 cells. A specific 5′-lipoxygenase inhibitor, A63162 inhibited PC3 and U937 proliferation. Some of these events are believed to represent components of "signal" transduction pathways responsible for reversible inhibition of DNA synthesis and the induction of partial phenotypic differentiation in competent cells. Arachidonic acid analogues which exert selective effects on physical and functional properties of cell membranes may represent an additional class of membrane-active agents with potential anticancer activity. A subset of their activities can be duplicated by inhibitors of 5′ lipoxygenase.

AB - ETYA (5,8,11,14-eicosatetraynoic acid), an arachidonic acid analogue, inhibited DNA synthesis in human transformed U937 (monoblastoid), PC3 (prostate) and A172 (glioblastoma) cells, and partially differentiated the U937 and A172 lines. The agent is not primarily cytotoxic at the concentrations employed, based upon exclusion of trypan blue, continued attachment of PC3 and A172 cells, unchanged release of Cr51, and reversibility of inhibited thymidine incorporation after removal of ETYA. Leukotriene C4 partially reversed the suppression of U937 DNA synthesis, suggesting its modulation by leukotrienes. U937 and A172 cells partially differentiated, as judged by a number of criteria. ETYA increased whole cell and microsomal membrane fluidity, increased intracellular Ca2+ in PC3 and U937 cells, altered the distribution and activity of protein kinase C in U937 cells, and rapidly downregulated the transcription of U937 c-myc. Evidence from transmission electron microscopy consistent with oxidative stress including putative lipofuscin bodies, myelin figures and disordered mitochondrial cristae and matrices was especially evident in PC3 cells, less so in A172 and essentially absent in U937 cells. A specific 5′-lipoxygenase inhibitor, A63162 inhibited PC3 and U937 proliferation. Some of these events are believed to represent components of "signal" transduction pathways responsible for reversible inhibition of DNA synthesis and the induction of partial phenotypic differentiation in competent cells. Arachidonic acid analogues which exert selective effects on physical and functional properties of cell membranes may represent an additional class of membrane-active agents with potential anticancer activity. A subset of their activities can be duplicated by inhibitors of 5′ lipoxygenase.

KW - AA

KW - ASA

KW - CAD

KW - CL

KW - DMSO

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KW - GFAP

KW - HPLC

KW - LTC 4

KW - PUFA

KW - SOD

KW - TLC

KW - TPN-DPH

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KW - arachidonic acid

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KW - computer-aided design

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KW - glial fibrillary acidic protein

KW - high-performance liquid chromatography

KW - leukotriene C4

KW - polyunsaturated fatty acid

KW - superoxide dismutase

KW - thin-layer chromatography

KW - trimethyl ammonium diphenylhexatriene

KW - unsaturated fatty acids (ETYA)

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ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells (2024)
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